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. 2021 Aug 16;131(16):e140527. doi: 10.1172/JCI140527

Figure 7. mHMGB1 mediated clearance of biofilm-resident NTHI, eradication of established mucosal biofilms, and resolution of experimental disease, an outcome that was enhanced upon codelivery with antibody fragments directed against the immunoprotective domains of a DNABII protein (tip-chimer Fabs).

Figure 7

(A) Study timeline to assess the relative ability of rHMGB1 or mHMGB1 to resolve NTHI biofilms already established in the chinchilla middle ear. (B) Relative quantity of NTHI resident within mucosal biofilms and adherent to the middle-ear mucosa 1 day after completion of therapy. (C) Rubric used to qualitatively assess the amount of middle-ear mucosal biofilm that remained 1 day after completion of treatment. (D) Relative amount of mucosal biofilm within each middle ear per cohort. (E) Rubric used to qualitatively assess the amount of middle-ear mucosal inflammation 1 day after completion of treatment. (F) Relative amount of mucosal inflammation within each middle ear per cohort. (G) Representative image of middle ears from each cohort to demonstrate relative presence or clearance of mucosal biofilm and inflamed or noninflamed state. (H) Study timeline to assess additive potential of mHMGB1 codelivered with tip-chimer Fabs to resolve NTHI biofilms already established in the chinchilla middle ear. (I) Relative quantity of NTHI resident within mucosal biofilms and adherent to the middle-ear mucosa 24 hours after 1 or 2 treatment doses. (J) Relative amount of mucosal biofilm within each middle ear per cohort 24 hours after 1 or 2 treatment doses. When delivered individually, both rHMGB1 and mHMGB1 induced rapid clearance of biofilm-resident NTHI and eradication of established mucosal biofilms, whereas only mHMGB1 induced limited mucosal inflammation. Moreover, codelivery of mHMGB1 with tip-chimer Fab fragments was highly efficacious to eradicate NTHI and associated biofilms from the middle ear. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ANOVA with Kruskal-Wallis multiple comparisons test (B); 1-way ANOVA with Tukey’s multiple comparison test (D, F, J); 1-way ANOVA with Holm-Sidak multiple comparison test (I).